A5102813737- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Immune Response and Inflammation
- Pneumonia and Respiratory Infections
- Chronic Kidney Disease and Diabetes
- Cell Adhesion Molecules Research
- Renal Diseases and Glomerulopathies
- Systemic Lupus Erythematosus Research
- Pneumocystis jirovecii pneumonia detection and treatment
- S100 Proteins and Annexins
- Endoplasmic Reticulum Stress and Disease
- Pancreatic function and diabetes
- Adipose Tissue and Metabolism
- Neonatal Respiratory Health Research
- COVID-19 Clinical Research Studies
- Adipokines, Inflammation, and Metabolic Diseases
- Neuroscience of respiration and sleep
- Blood disorders and treatments
- Chemotherapy-induced organ toxicity mitigation
- Vasculitis and related conditions
- Heme Oxygenase-1 and Carbon Monoxide
- Phagocytosis and Immune Regulation
- Cell death mechanisms and regulation
- Dialysis and Renal Disease Management
- Respiratory viral infections research
- Acute Kidney Injury Research
University of Louisville
2015-2024
Arkana Laboratories
2019
Our Lady of Bellefonte Hospital
2017
Providence Hospital
2017
University of Louisville Hospital
2017
Ashland (United States)
2017
Wenzhou Medical University
2009-2011
Colorado Kidney Care
2004
Medizinische Hochschule Hannover
2003
Max Delbrück Center
2003
Abstract Misfolded alpha-synuclein (AS) and other neurodegenerative disorder proteins display prion-like transmission of protein aggregation. Factors responsible for the initiation AS aggregation are unknown. To evaluate role amyloid made by microbiota we exposed aged rats transgenic C . elegans to E coli producing extracellular bacterial curli. Rats curli-producing bacteria displayed increased neuronal deposition in both gut brain enhanced microgliosis astrogliosis compared either mutant...
Abstract Respiratory burst activity and phosphorylation of an NADPH oxidase component, p47phox, during neutrophil stimulation are mediated by phosphatidylinositol 3-kinase (PI-3K) activation. Products PI-3K activate several kinases, including the serine/threonine kinase Akt. The present study examined ability Akt to regulate respiratory interact with phosphorylate p47phox. Inhibition in human neutrophils inhibitory peptide significantly attenuated fMLP-stimulated, but not PMA-stimulated,...
A comprehensive analysis of the role actin cytoskeleton in exocytosis four different neutrophil granule subsets had not been performed previously. Immunoblot showed that, compared with plasma membrane, there was less associated secretory vesicles (SV, 75%), gelatinase granules (GG, 40%), specific (SG, 10%), and azurophil (AG, 5%). Exocytosis SV, SG, AG measured as increased membrane expression CD35, CD66b, CD63, respectively, flow cytometry, GG release an ELISA....
Hyperglycemia induces p38 MAPK-mediated renal proximal tubular cell (RPTC) apoptosis. The current study hypothesized that alteration of the Akt signaling pathway by hyperglycemia may contribute to MAPK activation and development diabetic nephropathy. Immunoblot analysis demonstrated a hyperglycemia-induced increase in phosphorylation kidneys at 1 mo, peaking 3 dropping back baseline 6 mo. Immunohistochemical staining with anti-pAkt antisera localized tubules. Maximal was detected concomitant...
Abstract The role of exocytosis in the human neutrophil respiratory burst was determined using a fusion protein (TAT–SNAP-23) containing HIV transactivator transcription (TAT) cell-penetrating sequence and N-terminal SNARE domain synaptosome-associated protein-23 (SNAP-23). This agent inhibited stimulated secretory vesicles gelatinase specific granules but not azurophil granules. GST pulldown showed that TAT–SNAP-23 bound to combination vesicle-associated membrane protein-2 syntaxin-4 either...
Abstract Extensive evidence indicates that nutrient excess associated with obesity and type 2 diabetes activates innate immune responses lead to chronic, sterile low-grade inflammation, obese diabetic humans also have deficits in wound healing increased susceptibility infections. Nevertheless, the mechanisms sustain unresolved inflammation during remain unclear. In this study, we report saturated free fatty acids are elevated alter resolution of acute by promoting neutrophil survival...
Episodic hypoxia, a characteristic feature of obstructive sleep apnea, induces cellular changes and apoptosis in brain regions associated with neurocognitive function. To investigate whether mild, intermittent hypoxia would induce more extensive neuronal damage than similar degree sustained rat pheochromocytoma PC-12 cells were subjected to either (5% O(2)) or (alternating 5% O(2) 35 min, 21% 25 min) for 2 4 days. Quantitative assessment showed that while mild did not significantly increase...
Antineutrophil cytoplasmic antibodies (ANCA) activate human polymorphonuclear neutrophils (PMN) primed with tumor necrosis factor alpha (TNF-alpha) in vitro. Phosphatidylinositol 3-kinase (PI3-K) and the protein-serine/threonine kinase Akt have been implicated control of phagocyte respiratory burst. The hypothesis that PI3-K controls ANCA-induced burst was tested. TNF-alpha-primed PMN were stimulated a monoclonal antibody to myeloperoxidase (MPO) PR3- MPO-ANCA, respectively. activation...
Hypoxia is a common environmental stress that influences signaling pathways and cell function. Previous studies from our laboratory have identified significant differences in cellular responses to sustained or intermittent hypoxia with the latter proving more cytotoxic. We hypothesized susceptibility of neurons (IH) (SH) are mediated by altered Akt signaling. SH, but not IH, induced increase activation rat CA1 hippocampal region extracts compared room air controls. immunoprecipitations...
Abstract Serine/threonine kinase Akt, or protein B, has been shown to regulate a number of neutrophil functions. We sought identify Akt binding proteins in neutrophils provide further insights into understanding the mechanism by which regulates various Proteomic and immunoprecipitation studies identified γ-amino butyric acid (GABA) type B receptor 2 (GABABR2) as an human neutrophils. Neutrophil lysates subjected followed immunoblotting with anti-GABABR2 demonstrated association intact...
In the present study, novel preventive effects of repeated low-dose radiation exposure on diabetes-induced cardiac inflammation and damage were investigated. C57BL/6J mice given multiple low doses streptozotocin (STZ, 60 mg/kg × 6) to generate type 1 diabetes. A week after last STZ injection, hyperglycemic diagnosed treated with without whole-body (25 mGy X rays) once every 2 days for 2, 4, 8, 12 16 weeks. Diabetes caused significant increases in inflammation, shown by time-dependent mRNA...
Exocytosis of neutrophil granules contributes to acute lung injury (ALI) induced by infection or inflammation, suggesting that inhibition exocytosis in vivo could be a viable therapeutic strategy. This study was conducted determine the effect cell-permeable fusion protein inhibits (TAT-SNAP-23) on ALI using an immune complex deposition model rats. The intravenous administration TAT-SNAP-23 assessed albumin leakage, infiltration, histology, and proteomic analysis bronchoalveolar lavage fluid...
Hyperglycemia-induced renal fibrosis causes end-stage disease. Clopidogrel, a platelet inhibitor, is often administered to decrease cardiovascular events in diabetic patients. We investigated whether clopidogrel can reduce diabetes-induced streptozotocin-induced type 1 diabetes murine model and fibronectin involvement this protective response. Diabetic age-matched controls were sacrificed three months after the onset of diabetes, additional animals further treated with or vehicle for months....
Abstract The targets of the p38 MAPK pathway responsible for regulation neutrophil chemotaxis and exocytosis are unknown. One target this is actin-binding protein, heat shock protein 27 (Hsp27). Therefore, we tested hypothesis that Hsp27 mediates MAPK-dependent in human neutrophils through actin reorganization. Sequestration by introduction anti-Hsp27 Ab, but not an isotype inhibited fMLP-stimulated chemotaxis, increased cortical F-actin absence fMLP stimulation, exocytosis. Pretreatment...
Neutrophils play a significant role in determining disease severity following SARS-CoV-2 infection. Gene and protein expression defines several neutrophil clusters COVID-19, including the emergence of low density neutrophils (LDN) that are associated with severe disease. The functional capabilities these correlation gene unknown. To define host defense immunosuppressive functions normal (NDN) LDN from COVID-19 patients, we recruited 64 patients 26 healthy donors (HD). Phagocytosis,...
Parathyroid hormone inhibits sodium-phosphate cotransport in proximal renal tubule cells through activation of several kinases. We tested the hypothesis that activity these kinases was coordinated by an A kinase anchoring protein (AKAP) demonstrating type II cotransporter (NaPi-4) physically associated with AKAP and this association necessary for regulation phosphate transport parathyroid hormone. Immunoprecipitation anti-NaPi-4 antiserum glutathioneS-transferase pull-down GST-NaPi-4 showed...